Cleaning internal cavities is a difficult process. Large pipes, tanks, and other symmetrical cavities are mechanically cleaned by brushes, flails, and high pressure jets (e.g., liquid, gas, or steam). There is much poorer access to applying necessary mechanical action to smaller or complex-shaped internal cavities especially where materials transport becomes increasingly difficult. Brushes such as described by U.S. Pat. No. 5,931,845 to Amyette and dental flossers such as described by U.S. Pat. No. 5,855,216 to Robinson are designed to primarily remove material by direct mechanical contact where the contaminants are mostly removed by direct materials transfer, including scraping, displacement and the like. These methods require physical contact between a solid flexible member or element and the surface to be modified or cleaned, and are therefore limited to cleaning approximately cylindrical or accessible internal cavities.
Liquid/air jets as described by U.S. Pat. No. 6,192,900 to Arnal, et al. increase the cleanable areas of an internal cavity, but still require line of site accessibility from the jet orifice and a source of high pressure; therefore, the cleaning is always incomplete and in most cases requires complex alignment systems. Further, without the added presence of a moving solid member or element that could access the entire area to be cleaned, these liquid/jet cleaning methods have difficulty removing and homogenizing large debris such as blood clots, particulate materials, organic contaminants and the like. See U.S. Pat. No. 4,375,413 to Geel, et al. and U.S. Pat. No. 6,823,881 to Mishkin et al.
Multiple flow cleaning methods are described. For example, see U.S. Pat. No. 6,027,572 to Labib, et al., U.S. Pat. No. 6,326,340 to Labib, et al., U.S. Pat. No. 6,454,871 to Labib, et al., U.S. Pat. No. 6,619,302 to Labib, et al., U.S. Pat. No. 6,857,436 to Labib et al., U.S. Publication No. 2004/7255 to Labib, et al., and U.S. Pat. No. 6,945,257 to Tabani, et al. which are incorporated by reference herein. Multiple phase flow improves the cleanable areas of high-aspect ratio internal cavities, especially those with a high length/diameter (L/D) ratio, i.e., long and narrow spaces. Multiple phase flow can be complemented in large low-aspect ratio internal cavities with massive deposits, and wide and shallow spaces. Large low-aspect ratio designated cavities where L/D is small include hemodialyzer header space, hollow fiber modules headers, flat or curved surfaces where a cavity may be created to effect the cleaning of such surfaces, and the like.
Even though liquid/gas techniques can often access more of the internal surfaces better than moving solid devices alone, such as those described above, it would be beneficial if these methods could be combined. Liquid/gas flow inside cavities and spaces is insufficient to clean the same since such flow cannot generate sufficient shear stress to remove all the contaminants from all locations. It would be even more effective if this combination could be further improved to create optimal hydrodynamic flow fields within the cavity such that the generated mechanical stresses would be capable of completely cleaning the entire surfaces of internal cavities.
The theory of hydrodynamic flow and its effect on surface interactions has been elaborated for the case of a rotating disk. For example, see Cabin, et al., “Removal of Solid Organic Films From Rotating Disks Using Emulsion Cleaners,” J. of Colloid and Interface Sci., 228:344-358 (2000) and Yiantsios, et al., “Detachment of Spherical Microparticles Adhering on Flat Surfaces by Hydrodynamic Forces,” J. of Colloid and Interface Sci., 176:74-85 (1995). The theory of colloid mobilization was studied by Ryan, et al., “Colloid Mobilization and Transporting Ground Water,” Colloids and Surfaces, 107:1-56 (1996), using glass spheres or latex particles. There are few papers devoted to the removal of biocontamination. See Truskey, et al., “Relationship Between 3T3 Cell Spreading and the Strength of Adhesion on Glass and Silane Surfaces,” Biomater, 14(4):243-254 (1993), and Truskey, et al., “The Effect of Fluid Shear Stress Upon Cell Adhesion to Fibronectin-Treated Surfaces,” J. Biomed. Mater. Res. 24:1333-1353 (1990). However, these studies of basic theory have not been adapted or modified for cleaning the surfaces of internal cavities. In addition, such theories do not address the different flow patterns or modes of creating shear or other mechanical stresses in small cavities. It would be beneficial to extend hydrodynamic theory to the cleaning of poorly accessible internal surfaces such as in the case of hemodialyzer headers and the like.
Cleaning reusable dialyzer membranes is one application that needs improvement. Patients with End-Stage Renal Disease (ESRD) or who have acute or chronic renal failure, have kidneys that are incapable of removing waste products of metabolism and other substances from the blood and of excreting such undesirable substances in the urine. Patients with ESRD or persons who suffer from other forms of acute or chronic renal failure require dialysis treatments or kidney transplants. Only a small percentage of patients with renal failure are fortunate to receive kidney transplants, while the rest and the majority must undergo a form of dialysis treatment to purify their blood on a periodic basis.
Dialysis is defined as the process of cleaning wastes from the blood artificially. The two major forms of dialysis are hemodialysis and peritoneal dialysis. In hemodialysis, the blood travels through tubes to a dialyzer (also called hemodialyzer), which removes wastes and extra fluid from a patient's blood. The cleaned blood then flows through another set of tubes back to the body. This treatment can be performed three times per week, or even more times depending on the country and the healthcare system. In the year 2000, there were about 375,000 patients undergoing hemodialysis treatment and only about 40,000 receiving peritoneal treatment in the U.S. The number of patients requiring hemodialysis treatment is on the rise mostly because of the prevalence of Type II diabetes. The number of patients is increasing at a rate of about 8-10% per year. The number of patients requiring hemodialysis in the United States is expected to reach 600,000 by 2010. Hemodialysis treatment is the largest program funded by Medicare in the U.S. The majority of funding for dialysis treatment in the U.S. is in the form of reimbursement (e.g., $130/dialysis treatment/patient). Decreasing the cost of hemodialysis treatment is of paramount importance. It is also desirable to provide better overall treatment to dialysis patients while simultaneously improving the profitability of dialysis centers. A significant cost of hemodialysis treatment is the dialyzer which needs to be reprocessed to allow for multiple uses by the same patient. The number of treatments or uses of the same dialyzer is referred to as the “reuse number.” The practice of reusing dialyzers is permitted in the United States and many other countries. Dialyzer reuse is practiced in more than 70% of dialysis centers in the United States. Reuse is also beneficial because it cuts the amount of waste produced, which is both an economic (saves on the cost of disposal) and environmental (less waste) benefit. Since the dialyzer is not degradable and requires special biodisposal methods such as incineration, other environmental issues plus disposal costs are anticipated. It is therefore desirable to develop new methods and devices to achieve more efficient dialyzer reprocessing to reduce the cost and environmental impact, and at the same time to provide better-dialysis treatment for ESRD patients
The dialyzer is the device that effects the removal of fluids and wastes from a patient's blood. The dialyzer has two sections or compartments separated by a semi-permeable membrane. One section holds the dialysis solution (sometimes referred to as the dialysate) and the other holds the patient's blood. The dialyzer section that holds the dialysate is called the dialysate compartment and the section that holds the patient's blood is termed the blood compartment. The two compartments are in communication with each other through a semi-permeable membrane where waste substances such as urea and creatinine diffuse out from the blood side to the dialysate side of the dialyzer. Such diffusion and transport processes are the basis of dialysis treatment for patients that lack kidney function. The semi-permeable membranes of some types of dialyzers (termed high-flux dialyzers) are also capable of performing ultrafiltration, and this function is used to remove excess water from the patient's body during dialysis. By adjusting the pressure difference between the blood and dialyzer compartments with the aid of the dialysis machine, excess body water is removed during dialysis treatment.
In order to achieve dialysis treatment in a reasonable period of time, the membrane surface area of the dialyzer must be large enough to accomplish its task in the targeted time frame. A membrane surface area of approximately 1.5 to 2.5 square meters was found to be reasonable to achieve full dialysis treatment in about 3.5 to 4.4 hours. In order to package such a large membrane surface area in a dialyzer of a practical size, the hollow fiber membrane module configuration offers the optimal geometry. In this configuration, the membrane surface area needed is obtained by using a large number of small-diameter hollow fibers that are constructed from semi-permeable membranes.
A typical dialyzer has in excess of 12,000 of these hollow fibers, which are usually present in the form of a bundle of fibers (bundle diameter is about 3-5 cm) encased in a cylindrical rigid plastic shell, called a housing. During manufacturing, the extruded hollow fiber bundle is introduced into the rigid plastic shell housing and both ends of the fiber bundle are then embedded in a special polyurethane resin to completely fill the spaces between the fibers in the bundle and to seal the entire space with the plastic shell. After the resin is cured, the fiber bundle is cut on both ends of the plastic shell housing. Current manufacturing steps are designed to ensure that all fibers are open from both sides and that complete separation between the inside of fibers and the plastic shell housing is accomplished. The dialyzer is then outfitted with two headers or caps, one on each end, to provide access for the blood to flow into and out of the dialyzer during the dialysis treatment. These headers may be removable or made as a permanent part of the body of the dialyzer, depending on the manufacturer.
Each dialyzer is tested to satisfy the absolute condition of separation between the blood and dialysate compartments and other attributes; all testing is a part of the elaborate quality control process. Dialyzers cost between $12-30, depending on the type. Dialyzers are labeled either as “single use” or “for reuse (multiple uses).” Single-use dialyzers are discarded after each dialysis treatment, while reuse dialyzers are reprocessed after each dialysis session and reused by the same patient until they fail a critical criterion set by the FDA. On the average, a single-use high-flux dialyzer costs about $10-15 and a reuse high-flux dialyzer costs $25-30.
In reuse hemodialysis, a dialyzer is issued to the patient and reprocessed (cleaned and sterilized) after each dialysis treatment and then reused by the same patient until the dialyzer fails certain criteria set-forth by the FDA or additional criteria set by the dialysis center performing the treatment. Reuse dialyzers fail, or become unusable, for four basic reasons: (1) when the blood volume compartment of the dialyzer decreases to less than 80% of its new value, (2) if the dialyzer develops fiber leaks, (3) when the dialyzer's appearance becomes objectionable due to accumulated blood clots inside the fiber bundle or in the header region, or (4) when the number of reuses exceeds an arbitrary maximum reuse number set by the dialysis center. The FDA requires that reused dialyzers must have total cell volume or TCV (or blood volume inside the fiber bundle) above 80% that of a new dialyzer to ensure that 90% of urea is cleared during the treatment, that no fiber leaks occur during dialysis, and that the dialyzer be preserved in an approved liquid sterilant for more than 13 hours prior to the dialysis session to avoid subjecting the patient to microbial contamination. The dialyzer reuse number varies based on patient condition, reprocessing method, reagents used in reprocessing, protocol used to clean the header region (the pre-cleaning steps), and other factors, including the use of heparin during dialysis and handling the dialyzer after dialysis treatment. Dialyzer reuse practice is approved in the United States and Canada and in many countries in Asia and Latin America, but is not allowed in Japan and many European Union Countries, which adopt single-use dialysis where the dialyzer is disposed of after each treatment. Due to cost pressures, many countries are now practicing or considering adopting dialyzer reuse (reprocessing) to cut the cost of dialysis treatment.
Historically, the average dialyzer reuse number was about 3-5 when the reuse practice first started in the middle of the 1980s. This reuse number has increased in recent years by improving the dialyzer, preventing clotting during dialysis by heparinization and by adopting strict protocols to manually pre-clean the dialyzers prior to reprocessing them with automated devices. Many dialysis centers have instituted protocols to use heparin during dialysis to prevent the formation of blood clots inside the dialyzer (inside the fibers and header regions) during the dialysis session. Other dialysis centers require infusing a certain volume of heparin solution into the dialyzer immediately after the conclusion of treatment to minimize the formation of blood clots in the dialyzer until it is reprocessed. In addition, protocols now call for reprocessing the dialyzer within a short period of time after the treatment, usually two hours. All these attempts are made to increase the average reuse number of hemodialyzers.
Manual pre-cleaning of the dialyzer before reprocessing it with an automated device has been a very significant parameter responsible for improving the number of reuses, currently in the range of 8-15. This manual pre-cleaning of the dialyzer is an essential step that is needed prior to reprocessing with a peracetic acid liquid sterilant such as Renalin®, or other types of reprocessing, including the bleach formaldehyde process. Peracetic acid is known to denature blood proteins and increase the adhesion of blood components to the internal surfaces of the dialyzers, including the surfaces of hollow fibers, the header region cavity, as well as the O-ring that is present in dialyzers that have removable end caps. Current industry standard reprocessing devices, such as the Renatron® made by Minntech Corporation, do not have the capability to effectively clean the header region of a dialyzer. Due to these limitations, manual header cleaning is practiced to remove residual blood from the dialyzer by introducing reverse osmosis water into the fiber bundle and by using backflushing where water enters the blood compartment by pressurization of the dialysate compartment. Usually such cleaning does not follow a specific protocol and is left to the discretion of the technician.
An important step in reprocessing the dialyzer is manual pre-cleaning, which involves removing a range of blood clots from the header region of the dialyzer. Without removing such clots, the dialyzer cannot be successfully reprocessed, and will have a greater chance of failing prematurely for one of the 4 reasons stated above, specifically appearance and TCV. Header cleaning is possibly the most demanding step in pre-cleaning the dialyzer before using automated reprocessing machines. It requires, in many instances, hitting or impacting the external sides of the dialyzer end cap with a hard blunt object in order to dislodge blood clots present inside the header region of the dialyzer. A rawhide mallet tends to be the tool of choice. In some cases, reprocessing technicians often introduce “unsterile or contaminated” foreign objects inside the header to remove stubborn blood clots, and in most cases the same object is used to handle the dialyzers of multiple patients. A paperclip is a known object that is used to carry out this job. This kind of intervention has the potential of compromising the integrity of the dialyzer and increases the risk of cross infection between hemodialysis patients. Furthermore, in many cases the header is removed and the dialyzer and its cap are cleaned separately to remove blood clots. This practice is now discouraged due to the occurrence of an incident where 18 patients fell very ill, and where the CDC determined that this episode was due, to microbial contamination due to removing the header of the dialyzer during reprocessing. This incident and the associated practice are now known as “Header Syndrome.” Inability to remove blood from the dialyzer headers prior to reprocessing results in low reuse numbers. Blood clots in dialyzer headers are formed during dialysis treatment due to accumulation and stagnation of a volume of blood over an extended period of time, about three to four hours.
The presence of O-rings in some dialyzer models, such as Fresenius® F80A and F80B, and Optiflux® 180A, 180B, 200A and 200B introduces additional difficulties during reprocessing since blood clots could be entrapped behind or underneath the O-ring. Additionally, such O-rings create areas of dead flow that hamper effective cleaning of the header. To overcome this problem, the technician often removes the end cap and O-ring and cleans the end cap, O-rings, and puttied dialyzer surface manually. Due to the complex nature of blood clotting inside dialyzer headers, both manual and automated pre-cleaning devices, such as the RenaClear® made by Minntech Corporation, have many limitations, and this problem has been rendered even more complicated due to the fact that different dialyzer models have different header geometry. To complicate the issue, recent dialyzer designs have moved away from removable end caps, and dialyzers with O-ring-free headers are molded with the outer shell and thus cannot be removed during manual cleaning.
Blood clots inside the dialyzer header have many adverse consequences that influence the probability of successfully reprocessing the dialyzer and making it reusable. If the header contains large clots that cannot be removed or cleaned during the pre-cleaning step, subsequent reprocessing with one of the current devices, such as the Renatron® (made by Minntech Corporation, Minneapolis, Minn.) or the Seratronics® (made by Fresenius Medical Care, Lexington, Mass.) will not be successful. Often, the total cell volume of such dialyzers cannot be recovered to the FDA-required 80% level. When significant header clots are present during automated reprocessing, it is impossible to pass liquids through the hollow fibers because the openings of such fibers are blocked by blood clots in the header regions. This obstruction may be present on the inlet, the outlet, or both sides of the hollow fiber bundle, i.e., the venous side, arterial side, or both.
Dialyzers with highly clotted headers are so difficult to reprocess that in many cases they are discarded even without attempting to pre-clean them, let alone reprocess them. According to protocols adopted by many dialysis centers, the unacceptable appearance of a dialyzer due to the presence of large blood clots in the headers is sufficient to fail the dialyzer. Therefore, the presence of blood clots in the header region of the dialyzer constitutes a major problem that demands innovative methods and devices to overcome. The labor cost expended in pre-cleaning dialyzer headers is considerable and the risk of exposing reprocessing technicians to patient materials and infection needs to be eliminated, or greatly minimized.
Attempts to find a satisfactory means of cleaning the dialyzer header region can be complex, costly and time consuming. The RenaClear® device, manufactured by Minntech Corporation, is an example of such a device. This complicated and expensive device performs the header pre-cleaning steps as described by U.S. Pat. No. 6,192,900 to Arnal, et al. Using the RenaClear® device involves attaching the dialyzer to a device that introduces a jet of liquid from a needle where the jet is propelled with a stream of air. The jet is applied intermittently with the position of the jet direction changing with the aid of a motor. The jet action effects dislodging of blood clots due to the mechanical impact forces of the liquid, and the dislodged clots inside the header are then removed through a fluid path around the needle, again with the action of air/suction.
The RenaClear® device uses a peracetic acid solution to clean the header; such a process may require several minutes to perform, including attaching and detaching the dialyzer. The action of the jet is not very precise due to the geometrical complexity of the header and the possibility of bending the needle during handling. If the needle is bent, the direction/trajectory of the jet becomes less precise and the cleaning achieved becomes sub-optimal. In addition, cleaning of the entire internal surface of the header is impossible due to shadowing effects of obstructions inside the header, such as the O-ring, and to directional distortion due to the bending of the needle. An example of shadowing effects is exemplified by lack of cleaning in the regions that are shadowed by the O-ring, including the O-ring itself. Moreover, the RenaClear® device may be a source of contamination where blood clots can be forced to enter underneath and become lodged behind the O-ring due to the action of the jet, or in some cases even moved to other locations of the header and re-deposited. A major problem with the RenaClear® device is often associated with “bending the needle” during use, and this is due to the difference in header dimensions (tolerance) and frequent manipulation of the device, which involves attaching and detaching the dialyzer before actual reprocessing. In addition to the time consumed during header cleaning, the RenaClear® device requires the use of additional peracetic acid reagent during this pre-cleaning step, further adding to the cost of dialyzer reprocessing.
After subjecting the dialyzer to pre-cleaning using manual cleaning or the RenaClear® device, the dialyzer is removed and then installed for reprocessing with the Renatron® device, which performs the remaining tasks of reprocessing the dialyzer, including measuring TCV, testing for fiber leaks and filling the dialyzer with the peracetic acid liquid sterilant. The practice of installing and removing the dialyzer from two devices requires additional labor and time. This adds to reprocessing time, labor cost, and additional costs due to the use of reprocessing liquids and RO water. This is in addition to the high capital and maintenance costs of two separate devices for reprocessing the dialyzer.
It would be beneficial to find a better way to properly, repeatedly and consistently clean the headers of dialyzers and other difficult-to-access internal cavities found in applications such as water treatment, industrial processing, filtration, housings, in-line processing, bioprocessing, medical and dental devices, sensors, food processing, manufacturing and the like.